HIV disease is the leading cause of death among Americans aged 25 to 44. Although recent medical advances have made it possible to maintain tighter control of viral replication, allowing people with HIV to live longer, healthier lives, the complexity of antiretroviral (ARV) drug regimens and drug side effects make medicaiton adherence problematic. Moreover, deviations from the prescribed regimen may allow the virus to resume rapid replication and drug resistant mutations to develop that could render the prescribed drugs useless. Thus, poor adherence is one of the most pressing behavioral problems in the clinical management of HIV positive persons. The primary objective of the proposed 4-year project is to conduct a randomized clinical trial to evaluate the efficacy of a 6-month, theory-based behavioral intervention to enhance adherence to antiretroviral treatment regimens. We will recruit 216 participants frm among patients receiving clinical services at the UAB Outpatient HIV Clinic who are initiating a new antiretroviral regimen. Participants will be randomized either to a Standard Adherence Promtion condition or to an Enhanced Adherence Promotion condition that systematically addresses specific psychosocial issues associated with medication adherence. Medical mangement of study participants will be independent of group assignment. The primary outcome measure to evaluate adherence will be pill counts for antiretroviral medications. The secondary outcome measure will be viral load. Additional measures will include self-reported adherence to antiretroviral, CD4 count, and genotypic viral resistance. HIV related attitudes, depressive symptoms, coping strategies, and social support will also be assessed to examine theoretical assumptions regarding the causal relationship between psychosocial constructs and medication adherence. Outcome measures will be collected at baseline and at weeks 2, 4, 6, 8, 12, 16, 20, and 24. This application brings together a strong group of investigators with a history of individual and collaborative research relevant to the conduct of proposed interdisciplinary study examining the medical and behavioral management of HIV disease.